Sjögren Syndrome

Sjögren syndrome is a systemic autoimmune disorder whose clinical presentation is usually dominated by dryness of the eyes and mouth due to immune-mediated dysfunction of the lacrimal and salivary glands.

The disorder is predominantly seen in women, with a ratio of 9:1; most cases develop between the ages of 40 and 60 years.

Sjögren syndrome can occur in isolation (“primary” Sjögren syndrome) or in association with another rheumatic disease.

Sjögren syndrome is most frequently associated with rheumatoid arthritis but also occurs with SLE, primary biliary cholangitis, systemic sclerosis, polymyositis, Hashimoto thyroiditis, polyarteritis, and interstitial pulmonary fibrosis.

Diagnostic Essentials

• Women (average age 50 years) comprise 90% of patients.
• Dryness of eyes and dry mouth (sicca components) are the most common features; they occur alone or with rheumatoid arthritis or other connective tissue disease.
• Rheumatoid factor and antinuclear antibodies are common.
• Increased incidence of lymphoma.

Clinical Findings

Symptoms and Signs

Keratoconjunctivitis sicca results from inadequate tear production caused by lymphocyte and plasma cell infiltration of the lacrimal glands.

Ocular symptoms are usually mild. Burning, itching, and the sensation of having a foreign body or a grain of sand in the eye occur commonly.

For some patients, the initial manifestation is the inability to tolerate wearing contact lenses.

Many patients with more severe ocular dryness notice ropy secretions across their eyes, especially in the morning.

For most patients, symptoms of dryness of the mouth (xerostomia) dominate those of dry eyes. Patients frequently complain of a “cotton mouth” sensation and difficulty swallowing foods, especially dry foods like crackers, unless they are washed down with liquids. The persistent oral dryness causes most patients to carry water bottles or other liquid dispensers from which they sip constantly.

A few patients have such severe xerostomia that they have difficulty speaking. Persistent xerostomia results in rampant dental caries; caries at the gum line strongly suggest Sjögren syndrome.

Some patients are most troubled by loss of taste and smell.

Parotid enlargement, which may be chronic or relapsing, develops in one-third of patients.

Dryness may involve the nose, throat, larynx, bronchi, vagina, and skin.

Systemic manifestations include dysphagia, small-vessel vasculitis, pleuritis, obstructive airways disease and interstitial lung disease (in the absence of cigarette smoking), neuropsychiatric dysfunction (most commonly peripheral neuropathies), and pancreatitis; they may be related to the associated diseases noted above.

Renal tubular acidosis (type I, distal) occurs in 20% of patients.

Chronic interstitial nephritis, which may cause impaired kidney function, may be seen.

Laboratory Findings

Laboratory findings include mild anemia, leukopenia, and eosinophilia.

Polyclonal hypergammaglobulinemia, rheumatoid factor positivity (70%), and antinuclear antibodies (95%) are all common findings.

Antibodies against SS-A and SS-B are often present in primary Sjögren syndrome and tend to correlate with the presence of extraglandular manifestations (Table 1–7ck).

Useful ocular diagnostic tests include the Schirmer test, which measures the quantity of tears secreted.

Lip biopsy, a simple procedure, reveals characteristic lymphoid foci in accessory salivary glands.

Biopsy of the parotid gland should be reserved for patients with atypical presentations such as unilateral gland enlargement that suggest a neoplastic process.

Differential Diagnosis

Isolated complaints of dry mouth are most commonly due to medication side effects.

Chronic hepatitis C can cause sicca symptoms and rheumatoid factor positivity; minor salivary gland biopsies reveal lymphocytic infiltrates but not to the extent of Sjögren syndrome, and tests for anti-SS-A and anti-SS-B are negative.

Diffuse infiltration of CD8 T cells producing parotid gland enlargement can develop in HIV-infected individuals.

Involvement of the lacrimal or salivary glands, or both, in sarcoidosis can mimic Sjögren syndrome; biopsies reveal noncaseating granulomas.

IgG4-related systemic disease can cause lacrimal and salivary gland enlargement that mimics Sjögren syndrome.

Treatment and Prognosis

Treatment of sicca symptoms is symptomatic and supportive.

Artificial tears applied frequently will relieve ocular symptoms and avert further desiccation.

Topical ocular 0.05% cyclosporine also improves ocular symptoms and signs of dryness.

The mouth should be kept well lubricated. Sipping water frequently or using sugar-free gums and hard candies usually relieves dry mouth symptoms.

Pilocarpine (5 mg po qid) and the acetylcholine derivative cevimeline (30 mg po tid) may improve xerostomia symptoms.

Atropinic (anticholingeric) drugs and decongestants decrease salivary secretions and should be avoided.

A program of oral hygiene, including fluoride treatment, is essential to preserve dentition.

If there is an associated rheumatic disease, its systemic treatment is not altered by the presence of Sjögren syndrome.

Extraglandular disease, including arthritis, vasculitis, or pulmonary manifestations, is treated with similar immunosuppressive medications as SLE or rheumatoid arthritis.

Although Sjögren syndrome may compromise patients’ quality of life significantly, the disease is usually associated with a normal life span.

Poor prognoses are influenced mainly by the presence of systemic features associated with underlying disorders, the development in some patients of lymphocytic vasculitis, the occurrence of a painful peripheral neuropathy, and the complication (in a minority of patients) of lymphoma.

Severe systemic inflammatory manifestations are treated with prednisone or various immunosuppressive medications.

The patients at greatest risk for developing lymphoma are those with severe exocrine dysfunction, marked parotid gland enlargement, splenomegaly, vasculitis, peripheral neuropathy, anemia, and mixed monoclonal cryoglobulinemia (3–10% of the total Sjögren population).

When to Refer

• Presence of systemic symptoms or signs.
• Ocular dryness not responsive to artificial tears.

When to Admit

Presence of severe systemic signs such as vasculitis unresponsive to outpatient management.